The K05 award will provide Dr. Thomas L Vaughan with protected time (30% FTE) to continue to pursue key research questions related to the etiology and prevention of esophageal adenocarcinoma (EA), a cancer that has undergone a remarkable increase in incidence (6-fold overall, and 10-fold among white males) in the US and many western countries during the past four decades. It will also provide for protected time (20% FTE) to continue his extensive mentoring activities of students, postdoctoral fellows and junior investigators at the University of Washington (UW), the Fred Hutchinson Cancer Research Center (FHCRC) and outside institutions. The first four years of his current award (July 2007 - October 2011) provided critical protected time for him to focus on further developing and strengthening his research program on EA. Aim 1 of the current award funds his effort on analyses of previously-collected data and biospecimens from local studies with expired funding. This concentrated effort has thus far resulted in 20 published papers, and eight submitted manuscripts, many involving his direct supervision of pre- and postdoctoral mentees. Dr. Vaughan was one of the co-founders of the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) in 2005, supported in part by NCI. He was elected as first Steering Committee Chair and continues in that role. Aim 2 of the current award involves establishing BEACON as an important nexus for research on etiology and prevention of EA. During the first four years of the current award, membership in the consortium has approximately doubled, with annual workshops typically involving 40-50 attendees. Additional expertise in clinical gastroenterology, molecular biology, physiology, genetics, evolutionary biology and population genetics has been added to significantly expand the range of expert skill and knowledge available to plan and carry out new studies. Six research projects have been by grants from the NCI, NIDDK, Cancer Research UK, and the Swedish Cancer Society. Over the past two years, a further six manuscripts have been published or submitted and several more are in the final phases of development. Aim 3 of the current award involves development of new collaborative research projects within BEACON. The award allowed Dr. Vaughan to develop a multiple PI grant (funded in late 2009) for a genome-wide association study involving 14 sites and about 8,500 participants. The K05 award was key in providing not only protected time to develop this logistically-complicated grant application, but important training opportunities for Dr. Vaughan in genetic epidemiology (e.g., Welcome Trust conference on genetics of common diseases; invited participation at the Illumina Americas Scientific Summit and as a visiting scholar at Queensland Institute of Medical Research.) Proposed research activities during the renewal period represent a direct evolution of ideas and projects developed during the current K05 award period. The first aim will utilize the rich data resources of BEACON to develop risk and prediction models which are tailored to the absolute risk of specific populations that will be useful for a) health policy development, b) education, c) clinical decision-making, and d) designing future research. This aims address critical barriers to EA control by facilitating improvement in the costs and effectiveness of EA prevention interventions by ensuring that they make optimum use of knowledge regarding risk factors, protective factors and biomarkers that predict neoplastic progression, response to therapy and survival. The second aim encompasses his continued scientific leadership role in BEACON. Specifically this involves developing and actively participating in ongoing and new pooled analyses with the Consortium members, including ongoing BEACON studies such as analysis of telomere length, IGF-related markers, and adipokines; as well as ancillary analyses to the ongoing genome-wide association study of BE and EA. It also involves developing new collaborative research projects with BEACON investigators and mentees that will take advantage of the diverse populations represented, along with existing banks of well-characterized tissues. Dr. Vaughan has a well-established track record of mentoring graduate students and postdoctoral fellows, as well as junior faculty in Epidemiology and related disciplines. He is Director of an NCI-funded Cancer Epidemiology and Biostatistics Training Grant which funds nine predoctoral and four postdoctoral trainees and runs the journal club. He guest lectures in established epidemiology courses, and has served on 29 master's thesis committees, and 26 doctoral dissertation committees. Mentoring activities funded by the K05 will include: i) those associated with his responsibilities on the training grant, ii) his ongoing mentoring of other trainees from Epidemiology and related departments, and iii) mentoring junior faculty at the UW, FHCRC and outside institutions. Each year, he plans to work closely with two to three predoctoral students, one to two postdoctoral fellows; and one to two junior faculty members.